L-lysine : properties, uses, pros, cons, safety

L-lysine, an essential amino acid for humans, is widely used as a food supplement, for the composition of pharmaceutical products and as a raw material for cosmetics and synthetic materials and is primarily produced by microbial fermentation (e.g. Corynebacterium glutamicum, Escherichia, Streptomyces). It is also used in animal feed.

It is an α-amino acid.

Amino acids play a key metabolic function in the human body and are constituents of proteins. 

As food additives they perform different functions: preservatives, flavour enhancers, food supplements and more.

Amino acids together with their salts are used in cosmetics as conditioning agents for both hair and skin (e.g. as moisturisers and other similar functions). Moisturisers are different in nature: the best are the natural ones that exploit the mechanism of integration between the ingredient and the skin by moisturising the horny hydrolipid film, i.e. the thin protective layer that covers the epidermis protecting it from harmful external microbes, keeping the skin moisturised and supple and its pH or acidity value between 4 and 6.  Then there are the occlusive moisturisers, usually derived from petroleum (Paraffinum, Paraffinum liquidum and others), but also triglycerides, lanolin oil, natural or synthetic waxes, fatty acid esters and others that create an artificial occlusive layer on the stratum corneum of the skin with the advantage of accelerating the protective process but with the disadvantage of preventing the skin's natural transpiration.

α-amino acids that have similar physical structures undergo similar changes with regard to solubility in water/ethanol mixtures, and technologies to separate α-amino acids from industrial residues, which may not even be innocuous, are constantly being improved. However, many data on the solubility in water-ethanol and ethanol of some α-amino acids are contradictory or even lacking, and the effects of ethanol on the solubility of amino acids may be different. Overall, the scientific literature considers that α-amino acids do not pose significant problems for human health when taken orally, except in people with certain genetic diseases.

The difference between lysine and L-lysine is mainly terminological and stereochemical.

Lysine
It is a generic term that refers to the amino acid lysine without specifying its stereochemical form. In theory, it may include both the L form and the D form.

L-lysine
It is the biologically active form of lysine, the one naturally present in proteins and used by the human body for protein synthesis and metabolic functions.

In practice: when referring to nutrition, supplementation, or physiology, lysine = L-lysine. The distinction becomes relevant only in a chemical or stereochemical context.

Food safety: amino acid α generally considered safe.

Cosmetic safety: amino acid α generally considered safe when formulated to be non-irritant.

What it is used for and where

Medical

It promotes proper tissue function, growth and healing and improves the immune system, stimulates calcium absorption. It also appears to be active in the fight against herpes simplex.

A neuroprotective activity of L-lysine has been observed that confers neuroprotection after intracerebral haemorrhage injury by improving M2 microglial polarization and reducing inflammatory response in mice (1).

L-lysine plays a protective role in the toxicity of high glucose levels by counteracting hyperglycemia which is a characteristic element of diabetes, normally associated with protein glycation (2).

The intake of L-Lysine, given its recent spread as a dietary supplement, has revealed some subjective contraindications to its use. Most of these contraindications concerned the gastrointestinal tract with disorders such as nausea, stomach pain, diarrhea. The provisional level of absence of observed adverse effects obtained on the basis of these gastrointestinal symptoms was estimated at 6000 mg/person per day (3).

The increasing frequency of infections in implantable devices has encouraged the search for biocompatible antimicrobial surfaces. poly-l-lysine has been shown to inhibit adhesion and bacterial proliferation on biomaterials (4).

The antibacterial activity of L-Lysine on the growth of bacterial contaminants in platelets stored at room temperature is also confirmed (5).

Cosmetics

It has a protective action on the skin and contributes to the optimal oligomerisation of cell membranes.

The most relevant studies on this ingredient have been selected with a summary of their contents:

L-lysine, studies

• Molecular Formula: C₆H₁₄N₂O₂
• Linear Formula :  H₂N(CH₂)₄CH(NH₂)CO₂H
• Molecular Weight: 146.19 g/mol
• CAS: 56-87-1
• EC Number: 200-294-2
• DSSTox Substance ID: DTXSID6023232
• MDL number MFCD00064433
• FEMA 3487
• Beilstein/REAXYS Number 1722531
• PubChem Substance ID 329752387

Synonyms: 

• lysine
• h-Lys-oh
• (2S)-2,6-diaminohexanoic acid
• Aminutrin
• L-Norleucine, 6-amino-
• Hexanoic acid, 2,6-diamino-, (S)-

References__________________________________________

(1) Cheng J, Tang JC, Pan MX, Chen SF, Zhao D, Zhang Y, Liao HB, Zhuang Y, Lei RX, Wang S, Liu AC, Chen J, Zhang ZH, Li HT, Wan Q, Chen QX.  l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury.  Exp Neurol. 2020 Jan 24;327:113214. doi: 10.1016/j.expneurol.2020.113214.

(2)  Ebrahimi SM, Bathaie SZ, Faridi N, Taghikhani M, Nakhjavani M, Faghihzadeh S. L-lysine protects C2C12 myotubes and 3T3-L1 adipocytes against high glucose damages and stresses.  PLoS One. 2019 Dec 19;14(12):e0225912. doi: 10.1371/journal.pone.0225912

Abstract, Hyperglycemia is a hallmark of diabetes, which is associated with protein glycation and misfolding, impaired cell metabolism and altered signaling pathways result in endoplasmic reticulum stress (ERS). We previously showed that L-lysine (Lys) inhibits the nonenzymatic glycation of proteins, and protects diabetic rats and type 2 diabetic patients against diabetic complications. Here, we studied some molecular aspects of the Lys protective role in high glucose (HG)-induced toxicity in C2C12 myotubes and 3T3-L1 adipocytes. C2C12 and 3T3-L1 cell lines were differentiated into myotubes and adipocytes, respectively. Then, they were incubated with normal or high glucose (HG) concentrations in the absence/presence of Lys (1 mM). To investigate the role of HG and/or Lys on cell apoptosis, oxidative status, unfolded protein response (UPR) and autophagy, we used the MTT assay and flow cytometry, spectrophotometry and fluorometry, RT-PCR and Western blotting, respectively. In both cell lines, HG significantly reduced cell viability and induced apoptosis, accompanying with the significant increase in reactive oxygen species (ROS) and nitric oxide (NO). Furthermore, the spliced form of X-box binding protein 1 (XBP1), at both mRNA and protein levels, the phosphorylated eukaryotic translation initiation factor 2α (p-eIf2α), and the Light chain 3 (LC3)II/LC3I ratio was also significantly increased. Lys alone had no significant effects on most of these parameters; but, treatment with HG plus Lys returned them all to, or close to, the normal values. The results indicated the protective role of Lys against glucotoxicity induced by HG in C2C12 myotubes and 3T3-L1 adipocytes.

(3)  Hayamizu K, Oshima I, Fukuda Z, Kuramochi Y, Nagai Y, Izumo N, Nakano M. Safety assessment of L-lysine oral intake: a systematic review.  Amino Acids. 2019 Apr;51(4):647-659. doi: 10.1007/s00726-019-02697-3.

Abstract. Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of L-lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCOhost as search databases, we comprehensively searched human studies on oral ingestion of L-lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of L-lysine in the selected studies was 16.8-17,500 mg/day, and the range of dosing period was 1-1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).

(4) Ghilini F, Rodríguez González MC, Miñán AG, Pissinis D, Creus AH, Salvarezza RC, Schilardi PL.  Highly Stabilized Nanoparticles on Poly-l-Lysine-Coated Oxidized Metals: A Versatile Platform with Enhanced Antimicrobial Activity.  ACS Appl Mater Interfaces. 2018 Jul 18;10(28):23657-23666. doi: 10.1021/acsami.8b07529.

Abstract. The increasing incidence of infections in implantable devices has encouraged the search for biocompatible antimicrobial surfaces. To inhibit the bacterial adhesion and proliferation on biomaterials, several surface functionalization strategies have been developed. However, most of these strategies lead to bacteriostatic effect and only few of these are able to reach the bactericidal condition. In this work, bactericidal surfaces were designed through the functionalization of titanium surfaces with poly-l-lysine (PLL) as the mediator for the incorporation of antimicrobial silver nanoparticles (AgNPs). This functionalization influences the adsorption of the particles on the substrate impeding the agglomeration observed when bare titanium surfaces are used, leading to a homogeneous distribution of AgNPs on the surfaces. The antimicrobial activity of this surface has been tested against two different strains, namely, Staphylococcus aureus and Pseudomonas aeruginosa. For both strains and different AgNPs sizes, the surface modified with PLL and AgNPs shows a much enhanced antimicrobial activity in comparison with AgNPs deposited on bare titanium. This enhanced antibacterial activity is high enough to reach bactericidal effect, a condition hard to achieve in antimicrobial surfaces. Importantly, the designed surfaces are able to decrease the bacterial viability more than 5 orders with respect to the initial bacterial inoculum. That means that a relative low load of AgNPs on the PLL-modified titanium surfaces reaches 99.999% bacterial death after 24 h. The results of the present study are important to avoid infections in indwelling materials by reinforcing the preventive antibiotic therapy usually dosed throughout the surgical procedure and during the postoperative period.

(5) Naghadeh HT, Sharifi Z, Soleimani S, Jamaat ZPM, Ferdowsi S.  Efficacy of ε-Poly-L-lysine as an Antibacterial Additive for Platelets Stored at Room Temperature.  Iran J Med Sci. 2017 Sep;42(5):509-511.